The prediction of the three-dimensional structures of the native state of
proteins from the sequences of their amino acids is one of the most important
challenges in molecular biology. An essential ingredient to solve this problem
within coarse-grained models is the task of deducing effective interaction
potentials between the amino acids. Over the years several techniques have been
developed to extract potentials that are able to discriminate satisfactorily
between the native and non-native folds of a pre-assigned protein sequence. In
general, when these potentials are used in actual dynamical folding
simulations, they lead to a drift of the native structure outside the
quasi-native basin. In this study, we present and validate an approach to
overcome this difficulty. By exploiting several numerical and analytical tools
we set up a rigorous iterative scheme to extract potentials satisfying a
pre-requisite of any viable potential: the stabilization of proteins within
their native basin (less than 3-4 \AA cRMS). The scheme is flexible and is
demonstrated to be applicable to a variety of parametrizations of the energy
function and provides, in each case, the optimal potentials.Comment: Revtex 17 pages, 10 eps figures. Proteins: Structure, Function and
Genetics (in press